Dengue virus (DENV) is the cause of dengue illness (dengue fever, dengue hemorrhagic fever and dengue shock syndrome), which is reported in hundreds of thousands of people each year. Dengue hemorrhagic fever is fatal in about 0.5% of cases. DENVs are a group of four closely related arboviruses represented by serotypes DENV-1, DENV-2, DENV-3, and DENV-4. In areas of high virus presence, all four of the DENV serotypes may be circulating simultaneously.
The four DENV serotypes are antigenically distinct, but related serologically. Thus, infection by one serotype does not provide protection from subsequent infections by other serotypes. Studies demonstrated that host developed antibodies directed to the first infecting serotype may have some affinity for a second infecting serotype and lead to enhancement of the ability of the second virus to infect the host.
Patients with dengue usually seek medical attention during the first 5 days of illness; when the virus is present in the blood and IgM antibodies are not yet detectable. Therefore, diagnostic tests highly rely on the ability to detect virus components such as viral RNA.
Identification of DENV through serological methods is complicated due to extensive cross-reactivity between flaviviruses. The level of circulating IgM is not uniform based on the type of infection. For example, infection by a second DENV serotype may show little to no IgM response, and its presence may be masked by circulating IgM from either prior DENV infection, or from infection by another flavivirus. Thus, in areas with high or epidemic transmission of multiple flaviviruses, identification of DENV may not be possible by serological methods.
Within each DENV serotype, there are 4-6 genotypes, which represent lineages that may differ from one another in approximately 5-10% of their genomes.
Thus, there is a need for compositions and methods for the specific detection of DENV in fluidic samples such as whole blood, plasma, or serum early during disease presentation that does not rely on antibody serology, yet is sufficiently specific enough to broadly detect multiple DENV serotypes.